T cell immunity to MHV 68, a murine gamma herpesvirus

T 细胞对 MHV 68（一种鼠伽马疱疹病毒）的免疫

• 批准号: 7075401
• 负责人: Marcia A Blackman
• 金额: $ 34.18万
• 依托单位: TRUDEAU INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7075401
• 关键词: B lymphocyte; CpG islands; Gammaherpesvirinae; Herpesviridae disease; Herpesviridae vaccine; MHC class I antigen; MHC class II antigen; active immunization; antigen presentation; cellular immunity; cytotoxic T lymphocyte; dendritic cells; flow cytometry; helper T lymphocyte; hybridomas; immune response; immunomodulators; laboratory mouse; latent virus infection; lung; macrophage; microorganism immunology; neutralizing antibody; vaccine development

DESCRIPTION (provided by applicant): The gamma-herpesviruses, including EBV and KSHV, are persistent, oncogenic human pathogens that are widely disseminated in the population and are associated with human disease ranging from infectious mononucleosis to several malignancies. An important goal is the development of preventative vaccines. We have taken advantage of an experimental model, murine gamma-herpesvirus-68 (MHV-68), to dissect early events in the viral infection, to characterize the cellular and humoral immune response, and to test vaccination strategies. Our earlier vaccination studies have shown that vaccination can reduce the lytic load, but have so far failed to prevent the establishment of latency. However, new preliminary data show that latent infection is established in the lung as early as three days after infection, suggesting that efficient vaccines must quickly target infectious virus and lytically- and latently-infected cells in the lung. Based on these observations and recent advances in the field of T cell memory, we hypothesize that vaccination strategies emphasizing pulmonary immunity to both lytic and latent antigens will generate strong protective immunity. In addition, preliminary data showing that the presence of neutralizing antibody at the time of infection greatly reduced the peak lytic load suggests that neutralizing antibody may augment protective cellular immunity by controlling viral titers during the protective recall T cell response. The goal of the current studies is to characterize epitope expression (Aim 1) and virus-specific T cells (Aim 2) during acute and latent MHV-68 infection. In Aim 3, we will build on this information and use this well-characterized viral model as a "proof of principal" test for epitope-based vaccination strategies for the gamma-herpesviruses.

描述（由申请人提供）：γ-疱疹病毒，包括 EBV 和 KSHV，是持久性致癌人类病原体，在人群中广泛传播，并与从传染性单核细胞增多症到多种恶性肿瘤等人类疾病相关。一个重要目标是开发预防性疫苗。我们利用实验模型鼠伽马疱疹病毒 68 (MHV-68) 来剖析病毒感染的早期事件，表征细胞和体液免疫反应，并测试疫苗接种策略。我们早期的疫苗接种研究表明，疫苗接种可以减少裂解负荷，但迄今为止未能阻止潜伏期的建立。然而，新的初步数据显示，潜伏感染最早在感染后三天就在肺部建立，这表明有效的疫苗必须快速针对肺部的传染性病毒以及溶解性和潜伏性感染的细胞。基于这些观察结果和 T 细胞记忆领域的最新进展，我们假设强调针对裂解抗原和潜伏抗原的肺部免疫的疫苗接种策略将产生强大的保护性免疫。此外，初步数据显示，感染时中和抗体的存在大大降低了峰值裂解负荷，这表明中和抗体可以通过在保护性召回T细胞反应期间控制病毒滴度来增强保护性细胞免疫。当前研究的目标是表征急性和潜伏 MHV-68 感染期间的表位表达（目标 1）和病毒特异性 T 细胞（目标 2）。在目标 3 中，我们将在此信息的基础上，使用这一特征明确的病毒模型作为基于表位的 γ-疱疹病毒疫苗接种策略的“原理证明”测试。